Since the initiation of this project we have begun to clinically evaluate a small number of patients with LAD-1 that have come to the NIH in the past few months as part of their yearly evaluation by the Laboratory of Infectious Disease/NIAID team. During these visits we have collected oral fluid samples and bacterial plaque in order to begin to characterize the microbial profile and tissue pathology in this patient population. To date we have performed laboratory studies focused on the microbial characterization of lesions of aggressive periodontitis in a small number of patients with LAD-1. Our initial studies involve microbial profiling using the Human Oral Microbe Identification Microarray (HOMIM), which allows for the simultaneous detection of about 300 of the most prevalent oral bacterial species, including those that are uncultivable. Our preliminary results suggest that both classical periodontal pathogens and bacteria not typically encountered in periodontal disease may be implicated in the initiation and pathogenesis of aggressive periodontitis in LAD patients. Further microbial studies from additional human subjects and appropriate control populations will help us characterize further the microbial profile in LAD-associated periodontitis. In parallel with the microbial studies we have begun to characterize the nature of the immune response in LAD-associated periodontitis. We would like to interrogate possible immune mechanisms that may contribute to tissue pathology in this patient population. For this purpose we have begun to measure the presence and levels of immune mediators associated with chronic inflammation and activation of tissue destructive mechanisms in saliva and gingival crevicular fluid (GCF). We plan to continue these studies on additional subjects with varying severity of LAD-associated periodontitis.